Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial imaging by positron emission tomography:: a first human study

In previous in vivo studies with mice, rats, cats and monkeys, we have demonstrated that [7-methyl-C-11]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([C-11]TMSX) is a potential radioligand for mapping adenosine A(2A) receptors of the brain by positron emission tomography (PET). In the present study, we studied the potential of [C-11]TMSX for myocardial imaging. Uptake of radioactivity by the heart was high and gradually decreased after an intravenous injection of [C-11]TMSX into mice. In metabolite analysis, 54% and 76% of the radioactivity in plasma and heart, respectively, were present as the unchanged form of [C-11]TMSX 60 min postinjection. The myocardial uptake was reduced by carrier-loading and by co-injection of an adenosine A(2A) antagonist CSC, but not by co-injection of an adenosine A(1) antagonist DPCPX. Pretreatment with a high dose of a non-selective antagonist theophylline also reduced the myocardial uptake of [C-11]TMSX. These findings demonstrate the specific binding of [C-11]TMSX to adenosine A(2A) receptors in the heart. Finally we successfully performed the myocardial imaging by PET with [C-11]TMSX in a normal volunteer. A graphical analysis by Logan plot supported the receptor-mediated uptake of [C-11]TMSX. Peripherally [C-11]TMSX was very stable in human: >90% of the radioactivity in plasma was detected as the unchanged form in a 60-min study. We concluded that [C-11]TMSX PET has the potential for myocardial imaging.